Topotecan With or Without Aflibercept in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed extensive stage small cell lung cancer

  • Progressive or recurrent disease following one (and only one) standard first-line platinum-containing regimen (cisplatin or carboplatin)

• Measurable or non-measurable disease per RECIST criteria

  • Disease must be outside a previously irradiated field OR a new lesion must be inside the irradiated field
  • Disease must be outside a previously resected area OR a new lesion must be present
• No known brain metastasis unless the metastasis has been treated and is stable for ≥ 3 months prior to study entry
• No leptomeningeal involvement or brain stem metastasis
• Zubrod performance status 0-1
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Serum creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
• Urine protein: creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Willing to provide smoking history
• No evidence of active infection
• No active bleeding
• No significant history of bleeding diathesis, including hemoptysis (½ teaspoon of hemoptysis within the past 3 months), or underlying coagulopathy

• No history of recent arterial embolic events, including any of the following:

  • Myocardial infarction
  • Cerebrovascular accident
  • Transient ischemic attack
  • Worsening of pre-existing angina within the past 6 months

• No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg)

  • History of hypertension allowed provided it is controlled on anti-hypertensive medications
• No history of congestive heart failure
• No history of encephalitis or encephalopathy of any cause
• No diverticulitis, gastrointestinal bleeding, or peptic ulcer within the past 3 months
• No known AIDS or HIV-1 associated complex
• No known history of immune or immunodeficiency disorders
• No unstable or pre-existing major medical conditions except for cancer-related abnormalities

• No other prior malignancy except for any of the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • In situ cervical cancer
  • Adequately treated stage I or II cancer currently in complete remission
  • Any other cancer from which the patient been disease-free for 5 years
• Concurrent chronic therapeutic doses of low molecular weight heparin allowed
• At least 21 days since prior and no concurrent radiotherapy and recovered
• At least 28 days since prior and no concurrent surgery (e.g., thoracic or other major surgeries) and recovered
• No prior bevacizumab or other anti-angiogenic therapies including, but not limited to, small molecule tyrosine kinase inhibitors

• No concurrent enzyme-inducing anticonvulsant drugs

  • Non-enzyme-inducing anticonvulsant drugs (e.g., Keppra) allowed
• Concurrent chronic oral anticoagulation therapy allowed provided INR is maintained in the therapeutic range (INR 2-3)